Details of a Researcher - Tsubota, Kazuo

Papers - Tsubota, Kazuo

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Simple and accurate alignment of toric intraocular lenses and evaluation of their rotation errors using anterior segment optical coherence tomography

Watanabe Kazuhiro, Negishi Kazuno, Torii Hidemasa, Saiki Megumi, Dogru Murat, Tsubota Kazuo

Japanese Journal of Ophthalmology 56 ( 1 ) 31 - 37 2012.01

ISSN 0021-5155

Purpose: To describe a new method of alignment of toric intraocular lenses (IOLs) and evaluation of their rotation errors using anterior segment optical coherence tomography (AS-OCT). Methods: Twenty-nine eyes of 22 patients who had cataract extraction and implantation of an acrylic toric IOL were included. The new AS-OCT method was used for the alignment of toric IOLs and evaluation of their rotation errors. These rotation errors were evaluated and compared with those measured using the internal map of a wavefront aberrometer. Results: The mean rotation error ± standard deviation (SD) of the toric IOLs evaluated by AS-OCT was 3.2 ± 2.2° and 3.2 ± 2.4° at 1 week and 1 month after surgery, respectively. The mean difference in the reference axis between the visits was 1.8 ± 2.1°. The mean difference between the rotation errors of the alignment axes measured by AS-OCT and the internal map was 2.5 ± 1.9° (P = 0.037). Conclusion: The current method is clinically useful not only for the accurate alignment of toric IOLs but also for evaluating their rotation errors. © Japanese Ophthalmological Society 2011.

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Vision preservation during retinal inflammation by anthocyanin-rich bilberry extract

Miyake Seiji, Takahashi Noriko, Sasaki Mariko, Kobayashi Saori, Tsubota Kazuo, Ozawa Yoko

Laboratory Investigation 92 ( 1 ) 102 - 109 2012.01

ISSN 0023-6837

Anthocyanin-rich bilberry extract, a plant-derived antioxidant, has been utilized as a popular supplement for ocular health worldwide. However, it is unclear whether this extract has any biological effect on visual function, and the mechanism for such an effect is completely unknown. In this study, we generated a mouse model of endotoxin-induced uveitis (EIU) that shows retinal inflammation, as well as uveitis, by injecting lipopolysaccharide. We pretreated the mice with anthocyanin-rich bilberry extract and analyzed the effect on the retina. Anthocyanin-rich bilberry extract prevented the impairment of photoreceptor cell function, as measured by electroretinogram. At the cellular level, we found that the EIU-associated rhodopsin decreased and the shortening of outer segments in photoreceptor cells were suppressed in the bilberry-extract-treated animals. Moreover, the extract prevented both STAT3 activation, which induces inflammation-related rhodopsin decrease, and the increase in interleukin-6 expression, which activates STAT3. In addition to its anti-inflammatory effect, the anthocyanin-rich bilberry extract ameliorated the intracellular elevation of reactive oxygen species and activated NF-B, a redox-sensitive transcription factor, in the inflamed retina. Our findings indicate that anthocyanin-rich bilberry extract has a protective effect on visual function during retinal inflammation. © 2012 USCAP, Inc All rights reserved.

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Neuroprotective effects of lutein in the retina

Ozawa Yoko, Sasaki Mariko, Takahashi Noriko, Kamoshita Mamoru, Miyake Seiji, Tsubota Kazuo

Current Pharmaceutical Design 18 ( 1 ) 51 - 56 2012.01

ISSN 1381-6128

Although a large variety of pharmaceutical therapies for treating disease have been developed in recent years, there has been little progress in disease prevention. In particular, the protection of neural tissue is essential, because it is hardly regenerated. The use of nutraceuticals for maintaining the health has been supported by several clinical studies, including cross-sectional and interventional studies for age-related macular disease. However, mechanistic evidence for their effects at the molecular level has been very limited. In this review, we focus on lutein, which is a xanthophyll type of carotenoid. Lutein is not synthesized in mammals, and must be obtained from the diet. It is delivered to the retina, and in humans, it is concentrated in the macula. Here, we describe the neuroprotective effects of lutein and their underlying molecular mechanisms in animal models of vision-threatening diseases, such as innate retinal inflammation, diabetic retinopathy, and light-induced retinal degeneration. In lutein-treated mouse ocular disease models, oxidative stress in the retina is reduced, and its downstream pathological signals are inhibited. Furthermore, degradation of the functional proteins, rhodopsin (a visual substance) and synaptophysin (a synaptic vesicle protein also influenced in other neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease), the depletion of brain-derived neurotrophic factor (BDNF), and DNA damage are prevented by lutein, which preserves visual function. We discuss the possibility of using lutein, an antioxidant, as a neuroprotective treatment for humans. © 2012 Bentham Science Publishers.

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Changes in dry eye diagnostic status following implementation of revised Japanese dry eye diagnostic criteria

Uchino Yuichi, Uchino Miki, Dogru Murat, Ward Samantha, Yokoi Norihiko, Tsubota Kazuo

Japanese Journal of Ophthalmology 56 ( 1 ) 8 - 13 2012.01

ISSN 0021-5155

Purpose: Our aim was to evaluate changes in dry eye diagnostic status following implementation of the new dry eye diagnostic criteria in Japan. Design: This was a multicenter cross-sectional study. Methods: We recruited 295 individuals (81 men, 214 women, average age 43.6 ± 14.3 years) seen for general ophthalmic checkup and dry eye examinations. Using results of the Schirmer I test, tear breakup time, and fluorescein and Rose Bengal staining, patients were diagnosed as having definite dry eye (DDE), probable dry eye (PDE), or as being normal according to both the old and new Japanese dry eye diagnostic criteria. Results: Mean ages of normal participants and patients with PDE and DDE were 37.0 ± 10.4, 41.7 ± 14.4, and 47.7 ± 15.3 years, respectively (p < 0.001). All 37 individuals diagnosed as normal following the old criteria were also diagnosed as normal with the new diagnostic criteria. Among the 60 patients diagnosed as PDE with the old criteria, 19 (31.7%) were diagnosed as normal and 41(68.3%) as PDE with the new diagnostic criteria. Of the 198 patients diagnosed with DDE following the old criteria, 59 (29.7%) were diagnosed as PDE and 139 (70.2%) as DDE with the new diagnostic criteria. There was no significant difference in dry eye severity index scores between the old and new diagnostic criteria. Conclusion: A shift in the final dry eye diagnostic status from DDE to PDE and from PDE to normal was observed with the implementation of the new dry eye diagnostic criteria, suggesting that patients at the severe end of the dry eye disease spectrum are now diagnosed as DDE disease under the new criteria. © Japanese Ophthalmological Society 2011.

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Comparison of stem cell sources in the severity of dry eye after allogeneic haematopoietic stem cell transplantation

Uchino Miki, Ogawa Yoko, Uchino Yuichi, Mori Takehiko, Okamoto Shinichiro, Tsubota Kazuo

British Journal of Ophthalmology 96 ( 1 ) 34 - 37 2012.01

ISSN 0007-1161

Aims: To compare the incidence and severity of dry eye (DE) after allogeneic haematopoietic stem cell transplantation (HSCT) according to the stem cell source. The authors specifically focused on patients who received bone marrow transplantation (BMT), peripheral blood stem cell transplantation (PBSCT) and cord blood transplantation (CBT). Methods: Ninety-nine HSCT recipients who were prospectively followed-up for at least 100 days at Keio University Hospital were recruited. Ophthalmological examinations included evaluation of ocular surface findings and tear dynamics. The data on systemic graft-versus-host disease were collected by chart review. Results: Of the 99 patients (BMT, 67; PBSCT, 18; CBT, 14), 42 developed DE or showed worsened pre-existing DE after HSCT; 31 (46.3%) BMT group; 8 (44.0%) PBSCT group; and 3 (21.4%) CBT group (p=0.78). The median onset time of DE tended to be later in the PBSCT group (474 days, range 95-1559) than in the BMT (287 days, range 67-1216) or CBT (168 days, range 33-481) group, but the difference was not significant (p=0.23). However, the proportion of patients with severe DE was significantly higher in the PBSCT group (N=7, 87.5%) than in the BMT (N=12, 38.7%) or CBT (N=1, 33.3%) group (p=0.04) and CBT showed the lowest among all three stem cell sources. Conclusion: The data in this study suggested that the severity and onset time of DE were affected by the stem cell source. Close attention must be paid to the development of late-onset severe DE in PBSCT recipients.

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Plasma separation from human blood using spiral microchannels for dry eye treatment

Morikawa Jumpei, Yasui Takao, Kaji Noritada, Okamoto Yukihiro, Tokeshi Manabu, Tsubota Kazuo, Baba Yoshinobu

464 - 466 2012

Acute visual field defect following vitrectomy determined to originate from optic nerve by electrophysiological tests

Uchida Atsuro, Shinoda Kei, Matsumoto Celso Soiti, Kawai Miho, Kawai Sayaka, Ohde Hisao, Ozawa Yoko, Ishida Susumu, Inoue Makoto, Mizota Atsushi, Tsubota Kazuo

Case Reports in Ophthalmology 3 ( 3 ) 396 - 405 2012

Purpose: To present our findings on the cause of an acute visual field defect (VFD) that developed in a patient on the day after vitrectomy for proliferative diabetic retinopathy. Case: A 50-year-old man complained of a blind area in the superior visual field that developed one day after vitrectomy. The patient had undergone uncomplicated vitrectomy for a long-duration vitreous hemorrhage associated with proliferative diabetic retinopathy. Residual vitreous hemorrhage hampered a clear view of the fundus. Goldmann perimetry showed a horizontal VFD in the superior field. The area corresponding to the VFD was examined by multifocal electroretinograms (mfERGs) and multifocal visual evoked potentials (mfVEPs). The amplitudes of the mfVEPs were reduced with prolonged implicit times especially when the superior hemifield was stimulated, while the amplitudes and implicit times were within the normal range when other parts of the visual field were stimulated. In addition, the full-field photopic ERGs and photopic negative responses were attenuated in the right eye. These findings suggested that the VFD did not originate from alterations in the retinal inner and middle layer but in the ganglion cells. The visual acuity improved to 1.2 but his optic disc became pale and the VFD remained unchanged more than 12 years after the surgery. Conclusion: We suggest that vitrectomy can cause ischemic optic neuropathy by interfering with the circulation associated with diabetes mellitus. Evaluations by mfERGs, mfVEPs, and full-field photopic ERGs were helpful in making the diagnosis. © 2012 S. Karger AG, Basel.

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Transpupillary thermotherapy for atypical central serous chorioretinopathy

Kawamura Ryosuke, Ideta Hidenao, Hori Hideyuki, Yuki Kenya, Uno Tsuyoshi, Tanabe Tatsurou, Tsubota Kazuo, Kawasaki Tsutomu

Clinical Ophthalmology 6 ( 1 ) 175 - 179 2012

ISSN 1177-5467

Background: Central serous chorioretinopathy (CSC) has been traditionally treated with laser photocoagulation. We thought that transpupillary thermotherapy (TTT) utilizing a lower temperature than that of conventional laser photocoagulation might minimize permanent retinal and choroidal damage. Studies suggest that undesirable effects on vision due to TTT are minimal even if it is applied to foveal and/or parafoveal lesions when TTT requires a larger irradiation spot. The aim of this study was to evaluate the efficacy of TTT in the management of atypical CSC. Methods: We defined atypical CSC as bullous retinal detachment with diffuse or several leakages, severe leakage with fibrin formation under serous retinal detachment, or leakage within a pigment epithelium detachment. Eight consecutive patients with atypical CSC underwent visual acuity testing, ophthalmic examination, color photography, fluorescein angiography, and optical coherence tomography to evaluate the results of transpupillary thermotherapy. Retreatment of atypical CSC was based on ophthalmic examination, optical coherence tomography, and fluorescein angiography. TTT was performed on the leaking spots shown in fluorescein angiography, with a power of 50-250 mW, spot size of 500-1200 μm, and exposure time of 13-60 seconds to minimize retinal damage. Results: In five of eight affected eyes, serous detachments completely resolved within 1 month after the initial TTT. One eye had persistent subretinal fluid and required a second TTT treatment. Two eyes showed no resolution of CSC and were treated by conventional photocoagulation. Initial best-corrected visual acuity (BCVA) ranged from 20/600 to 20/20 (mean, 20/40; median, 20/30). Final BCVA ranged from 20/200 to 20/20 (mean, 20/25; median, 20/20). BCVA improved in all cases. Only two eyes with persistent subretinal fibrin and existing retinal pigment epithelial alternations in macular area showed limited improvement of BCVA despite the absence of subretinal exudation. The presence of retinal attachment was confirmed by optical coherence tomography in six eyes (75%). Conclusions: TTT seems to be effective for the treatment of atypical CSC in the short term. Additional studies are necessary to evaluate the long-term effectiveness and safety. © 2012 Kawamura et al, publisher and licensee Dove Medical Press Ltd.

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Renin-angiotensin system hyperactivation can induce inflammation and retinal neural dysfunction

Kurihara Toshihide, Ozawa Yoko, Ishida Susumu, Okano Hideyuki, Tsubota Kazuo

International Journal of Inflammation 2012 2012

ISSN 2090-8040

The renin-angiotensin system (RAS) is a hormone system that has been classically known as a blood pressure regulator but is becoming well recognized as a proinflammatory mediator. In many diverse tissues, RAS pathway elements are also produced intrinsically, making it possible for tissues to respond more dynamically to systemic or local cues. While RAS is important for controlling normal inflammatory responses, hyperactivation of the pathway can cause neural dysfunction by inducing accelerated degradation of some neuronal proteins such as synaptophysin and by activating pathological glial responses. Chronic inflammation and oxidative stress are risk factors for high incidence vision-threatening diseases such as diabetic retinopathy (DR), age-related macular degeneration (AMD), and glaucoma. In fact, increasing evidence suggests that RAS inhibition may actually prevent progression of various ocular diseases including uveitis, DR, AMD, and glaucoma. Therefore, RAS inhibition may be a promising therapeutic approach to fine-tune inflammatory responses and to prevent or treat certain ocular and neurodegenerative diseases. © 2012 Toshihide Kurihara et al.

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Neuroprotective response after photodynamic therapy

Suzuki Misa, Ozawa Yoko, Kubota Shunsuke, Hirasawa Manabu, Miyake Seiji, Noda Kousuke, Tsubota Kazuo, Kadonosono Kazuaki, Ishida Susumu

Journal of Neuroinflammation 8 2011.12

Background: Anti-vascular endothelial growth factor (VEGF) drugs and/or photodynamic therapy (PDT) constitute current treatments targeting pathological vascular tissues in tumors and age-related macular degeneration. Concern that PDT might induce VEGF and exacerbate the disease has led us to current practice of using anti-VEGF drugs with PDT simultaneously. However, the underlying molecular mechanisms of these therapies are not well understood.Methods: We assessed VEGF levels after PDT of normal mouse retinal tissue, using a laser duration that did not cause obvious tissue damage. To determine the role of PDT-induced VEGF and its downstream signaling, we intravitreally injected a VEGF inhibitor, VEGFR1 Fc, or a PI3K/Akt inhibitor, LY294002, immediately after PDT. Then, histological and biochemical changes of the retinal tissue were analyzed by immunohistochemistry and immunoblot analyses, respectively.Results: At both the mRNA and protein levels, VEGF was upregulated immediately and transiently after PDT. VEGF suppression after PDT resulted in apoptotic destruction of the photoreceptor cell layer in only the irradiated area during PDT. Under these conditions, activation of the anti-apoptotic molecule Akt was suppressed in the irradiated area, and levels of the pro-apoptotic protein BAX were increased. Intravitreal injection of a PI3K/Akt inhibitor immediately after PDT increased BAX levels and photoreceptor cell apoptosis.Conclusion: Cytotoxic stress caused by PDT, at levels that do not cause overt tissue damage, induces VEGF and activates Akt to rescue the neural tissue, suppressing BAX. Thus, the immediate and transient induction of VEGF after PDT is neuroprotective. © 2011 Suzuki et al; licensee BioMed Central Ltd.

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Corneal damage and lacrimal gland dysfunction in a smoking rat model

Higuchi Akihiro, Ito Kaori, Dogru Murat, Kitamura Masanori, Mitani Fumiko, Kawakita Tetsuya, Ogawa Yoko, Tsubota Kazuo

Free Radical Biology and Medicine 51 ( 12 ) 2210 - 2216 2011.12

ISSN 0891-5849

Smoking is a serious public health problem around the world and causes many diseases such as chronic obstructive pulmonary disease, lung cancer, and some eye diseases. Cytochrome P450s (CYPs) are xenobiotic-metabolizing enzymes and are distributed in the corneas, protecting the ocular surface against chemical compounds in the environment. Although CYPs are principally detoxification enzymes, CYP1A1 and CYP2A6 are known to participate in the induction of lung cancer by smoking. We studied the participation of CYPs in corneal dysfunction caused by exposure to mainstream cigarette smoke (MCS) in a smoking rat model. Six-week-old male Sprague-Dawley rats were exposed to MCS. Exposure to MCS caused corneal damage and lacrimal gland dysfunction. Immunohistochemical analysis revealed that CYP1A1 expression was upregulated in the corneal epithelium and ducts of the lacrimal glands, accompanied by an increase in production of reactive oxygen species (ROS). An increase in 8-hydroxy-2′- deoxyguanosine, which is a marker of oxidative DNA damage, was detected only in areas where CYP1A1 was expressed, whereas the level of hexanoyl-lysine adduct, which is an initial marker of oxidative damage of phospholipids, did not increase. Exposure to MCS damaged the corneas and lacrimal glands probably through DNA oxidation by ROS produced by CYP1A1. Although the influence of other components in MCS remains unclear, CYPs, especially CYP1A1, probably participate in corneal damage and lacrimal gland dysfunction induced by smoking. © 2011 Elsevier Inc. All rights reserved.

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Generation of stratified squamous epithelial progenitor cells from mouse induced pluripotent stem cells

Yoshida Satoru, Yasuda Miyuki, Miyashita Hideyuki, Ogawa Yoko, Yoshida Tetsu, Matsuzaki Yumi, Tsubota Kazuo, Okano Hideyuki, Shimmura Shigeto

PLoS ONE 6 ( 12 ) 2011.12

Background: Application of induced pluripotent stem (iPS) cells in regenerative medicine will bypass ethical issues associated with use of embryonic stem cells. In addition, patient-specific IPS cells can be useful to elucidate the pathophysiology of genetic disorders, drug screening, and tailor-made medicine. However, in order to apply iPS cells to mitotic tissue, induction of tissue stem cells that give rise to progeny of the target organ is required. Methodology/Principal Findings: We induced stratified epithelial cells from mouse iPS cells by co-culture with PA6 feeder cells (SDIA-method) with use of BMP4. Clusters of cells positive for the differentiation markers KRT1 or KRT12 were observed in KRT14-positive colonies. We successfully cloned KRT14 and p63 double-positive stratified epithelial progenitor cells from iPS-derived epithelial cells, which formed stratified epithelial sheets consisting of five- to six-polarized epithelial cells in vitro. When these clonal cells were cultured on denuded mouse corneas, a robust stratified epithelial layer was observed with physiological cell polarity including high levels of E-cadherin, p63 and K15 expression in the basal layer and ZO-1 in the superficial layer, recapitulating the apico-basal polarity of the epithelium in vivo. Conclusions/Significance: These results suggest that KRT14 and p63 double-positive epithelial progenitor cells can be cloned from iPS cells in order to produce polarized multilayer epithelial cell sheets. © 2011 Yoshida et al.

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Correlation between contrast sensitivity and higher-order aberration based on pupil diameter after cataract surgery

Yamaguchi Takefumi, Negishi Kazuno, Ohnuma Kazuhiko, Tsubota Kazuo

Clinical Ophthalmology 5 ( 1 ) 1701 - 1707 2011.12

ISSN 1177-5467

Background: The purpose of this study was to evaluate the correlation between contrast sensitivity and calculated higher-order aberrations based on individual natural pupil diameter after cataract surgery. Methods: This prospective study included 120 eyes from 92 patients who were randomized to receive one of four lenses, including three aspheric lenses (Acrysof SN60WF, Tecnis ZA9000, and Hoya Py60AD) and one spherical lens (Acrysof SN60AT). Contrast sensitivity, higher-order aberrations of the whole eye, and pupil diameter under photopic and mesopic conditions were measured 1 month postoperatively. Higher-order aberrations were decomposed into Zernike coefficients, calculated according to individual pupil diameter. The correlation between higher-order aberrations and contrast sensitivity was evaluated. Results: There were no significant differences in contrast sensitivity function between the four types of lenses under photopic conditions. However, the contrast sensitivity function and area under log contrast sensitivity function in the aspheric lenses were significantly better than in the spherical lens under mesopic conditions. Under mesopic conditions, spherical aberration in eyes with aspheric lenses was significantly lower than in eyes with spherical lenses (P,<0.05). Under photopic conditions, coma aberration had a significant negative correlation with contrast sensitivity at 12 cycles/degree. Under mesopic conditions, spherical aberration had a significant negative correlation with contrast sensitivity at 3, 6, and 12 cycles/degree with glare, and with contrast sensitivity at 6 and 18 cycles/degree without glare. Conclusion: In terms of influence on visual function, coma aberration may be more significant under photopic conditions and spherical aberration under mesopic conditions. © 2011 Yamaguchi et al, publisher and licensee Dove Medical Press Ltd.

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Prevalence and risk factors of dry eye disease in Japan

Uchino Miki, Nishiwaki Yuji, Michikawa Takehiro, Shirakawa Kazuhiro, Kuwahara Erika, Yamada Mutsuko, Dogru Murat, Schaumberg Debra A., Kawakita Tetsuya, Takebayashi Toru, Tsubota Kazuo

Ophthalmology 118 ( 12 ) 2361 - 2367 2011.12

ISSN 0161-6420

Objective: To estimate the prevalence and risk factors of dry eye disease (DED) in a rural setting in Japan. Design: Cross-sectional study. Participants: We included 3294 subjects, aged <40 years who were in the residential registry for Koumi town. Intervention: Subjects in a rural mountain area, Koumi town, completed questionnaires designed to detect dry eye diagnosis and risk factors. Main Outcome Measures: Clinically diagnosed DED was defined as the presence of a previous clinical diagnosis of DED by ophthalmologists or severe symptoms of DED (both dryness and irritation constantly or often). Current symptoms of DED and possible risk factors such as age, gender, educational history, smoking history, alcohol drinking history, height and weight, visual display terminal (VDT) use, and contact lens (CL) wear, and past/current history of certain common systemic diseases were the main outcome measures. We used logistic regression analysis to examine associations between DED and other demographic factors. Results: Of the 3294 eligible residents, 2791 residents (85%) completed the questionnaire. The percentage of women with a composite outcome of clinically diagnosed DED or severe symptoms (21.6%; 95% confidence interval [CI], 19.523.9) was higher than that of men (12.5%; 95% CI, 10.714.5; P<0.001). A low body mass index (BMI; odds ratio [OR], 2.07; 95% CI, 0.984.39), CL use (OR, 3.84; 95% CI, 1.4610.10), and hypertension (HT) (OR, 1.39; 95% CI, 0.942.06) were risk factors for DED in men. Use of a VDT (OR, 2.33; 95% CI, 1.124.85), CL use (OR, 3.61; 95% CI, 2.136.10), and myocardial infarction or angina were the risk factors (OR, 2.64; 95% CI, 1.514.62), whereas high BMI was a preventive factor (OR, 0.69; 95% CI, 0.481.01) for DED in women. Conclusions: Among a Japanese cohort, DED leading to a clinical diagnosis or severe symptoms is prevalent. Use of CLs was a common dry eye risk factor in both genders. The condition is more prevalent in men with low BMI, HT, and in women with myocardial infarction or angina and VDT use. Relevant measures directed against the modifiable risks may provide a positive impact on public health and quality of life of Japanese. © 2011 by the American Academy of Ophthalmology.

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Corneal fluorescein staining correlates with visual function in dry eye patients

Kaido Minako, Matsumoto Yukihiro, Shigeno Yuta, Ishida Reiko, Dogru Murat, Tsubota Kazuo

Investigative Ophthalmology and Visual Science 52 ( 13 ) 9516 - 9522 2011.12

ISSN 0146-0404

Purpose. To investigate the changes in functional visual acuity (VA) and higher order aberrations in dry eye patients. Methods. In this prospective comparative case series, 22 right eyes were classified into those with or without superficial punctate keratopathy (SPK) in the central cornea of 22 patients with Sjögren syndrome; 10 right eyes of 10 normal subjects served as the control. Serial measurements of VAs using a functional VA measurement system and higher order aberrations using a wavefront sensor were performed under blink-free conditions without topical anesthesia over a 10-second period. The parameters for each measurement were compared among the SPK-positive and -negative and normal groups. The correlation between those parameters was also analyzed. Results. Dry eye with SPK showed significant deterioration of visual function and optical quality compared with dry eye without SPK and in normal eyes, as detected by both the visual maintenance ratio (VMR; P < 0.05) and the variation of VA (P < 0.05) and by comalike and total higher order aberrations (P < 0.05). Moreover, the severity of epithelial damage at the central cornea correlated significantly with VMR (P < 0.01) and variation of VA (P < 0.01) as well as comalike (P < 0.05) and total higher order aberrations (P < 0.05). The dry eye group without SPK showed minor visual deterioration compared with normal eyes, as detected only by VMR (P < 0.05). Conclusions. Optical disturbances at the central optical zone of the cornea in dry eye disease may affect visual performance. Functional VA measurement may be an applicable method of evaluating visual performance in dry eyes that is as efficient as wavefront aberration measurements. © 2011 The Association for Research in Vision and Ophthalmology, Inc.

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Inflammation after phakic implants

Torii Hidemasa, Negishi Kazuno, Dogru Murat, Saiki Megumi, Yamaguchi Takefumi, Watanabe Kazuhiro, Kato Naoko, Tsubota Kazuo

Ophthalmology 118 ( 12 ) 2011.12

ISSN 0161-6420

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The impact of contact lens wear and visual display terminal work on ocular surface and tear functions in office workers

Kojima Takashi, Ibrahim Osama M A, Wakamatsu Tais, Tsuyama Atsushi, Ogawa Junko, Matsumoto Yukihiro, Dogru Murat, Tsubota Kazuo

American Journal of Ophthalmology 152 ( 6 ) 2011.12

ISSN 0002-9394

Purpose: To evaluate the effect of contact lens (CL) wear and visual display terminal (VDT) work on the ocular surface and tear functions. Design: Prospective case-control study. Methods: Sixty-nine CL wearers (45 women and 24 men; mean age, 35.2 ± 7.3 years), and 102 age- and sex-matched non-CL wearers were enrolled in the study (66 women and 36 men; mean age, 36.7 ± 7.3 years). Ocular surface and tear function tests, including vital stainings (fluorescein and rose bengal), Schirmer test, tear meniscus height measurement, and tear film break-up time were performed. The subjective symptoms of dry eyes were evaluated using a dry eye symptom questionnaire. The participants were divided into 4 subgroups according to the total time of VDT work in 1 day (VDT work time in 1 day < 4 hours or < 4 hours) and presence of CL wear. Main outcome measures included ocular surface vital staining scores, Schirmer test results, tear film break-up time, tear meniscus height measurement, and symptom questionnaire score. Results: CL users and long-term VDT workers showed significantly worse tear meniscus height values than non-CL users and short-term VDT workers (P <.001). The mean visual symptom scores in CL wearers and long-term VDT workers were significantly higher than the other groups (P <.001). Conclusions: Office workers who wore CLs and spent more than 4 hours engaged in VDT work had a lower tear meniscus volume with significant dry eye and visual symptoms triggered by environmental factors. © 2011 Elsevier Inc.

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Miami to Japan eye-care rescue mission

Tsubota Kazuo, Yoshida Tsunehiko, Kurosaka Daijiro, Lee Richard K., Alfonso Eduardo C., Nakazawa Toru

American Journal of Ophthalmology 152 ( 5 ) 886 - 887 2011.11

ISSN 0002-9394

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Roles of AMP-activated protein kinase in diabetes-induced retinal inflammation

Kubota Shunsuke, Ozawa Yoko, Kurihara Toshihide, Sasaki Mariko, Yuki Kenya, Miyake Seiji, Noda Kousuke, Ishida Susumu, Tsubota Kazuo

Investigative Ophthalmology and Visual Science 52 ( 12 ) 9142 - 9148 2011.11

ISSN 0146-0404

Purpose. AMP-activated protein kinase (AMPK) is a sensor of cellular energy status. The purpose of the present study was to elucidate the roles of AMPK in the pathogenesis of diabetic retinopathy using the known AMPK activators resveratrol and AICAR (5-aminoimidazole-4-carboxamide ribonucleoside) in a mouse model. Methods. C57BL/6 mice with streptozotocin-induced diabetes were treated with resveratrol orally at 50 mg/kg for 7 days or with AICAR intraperitoneally at 100 mg/kg 24 hours before death. Retinal protein levels of phosphorylated and total AMPK, phosphorylated nuclear factor (NF)-κB p65, intercellular adhesion molecule (ICAM)-1, and vascular endothelial growth factor (VEGF) were evaluated by Western blot analysis or enzyme-linked immunosorbent assay. Retinal activity of sirtuin (SIRT)1 was measured by deacetylase fluorometric assay. Leukocyte adhesion to the retinal vasculature was examined with a concanavalin A lectin perfusion-labeling technique. Results. Induction of diabetes in mice led to retinal AMPK dephosphorylation, which was significantly reversed by either resveratrol or AICAR. Either resveratrol or AICAR significantly reversed SIRT1 deactivation and NF-κB phosphorylation, both of which were induced in the diabetic retina. Administration of resveratrol to diabetic mice significantly reduced diabetes-induced retinal leukocyte adhesion, together with retinal expression of ICAM-1 and VEGF. Conclusions. The present findings reveal that diabetes-induced retinal inflammation stems from downregulation of the AMPK pathway, leading subsequently to SIRT1 deactivation and NF-κB activation. The data also suggest the potential use of the AMPK activator resveratrol as a therapeutic agent for diabetic retinopathy. © 2011 The Association for Research in Vision and Ophthalmology, Inc.

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Effect of controlled adverse chamber environment exposure on tear functions in silicon hydrogel and hydrogel soft contact lens wearers

Kojima Takashi, Matsumoto Yukihiro, Ibrahim Osama M A, Wakamatsu Tais Hitomi, Uchino Miki, Fukagawa Kazumi, Ogawa Junko, Dogru Murat, Negishi Kazuno, Tsubota Kazuo

Investigative Ophthalmology and Visual Science 52 ( 12 ) 8811 - 8817 2011.11

ISSN 0146-0404

Purpose. To prospectively evaluate the effect of controlled adverse chamber environment (CACE) exposure on tear function, including tear osmolarity, in subjects wearing narafilcon A versus those wearing etafilcon A soft contact lens (SCL). Methods. Thirty-one healthy subjects with no history of contact lens wear (13 women, 18 men; average age, 30.5 ± 6.5 years) were randomly divided into age- and sex-matched groups (15 subjects wearing narafilcon A SCL; 16 subjects wearing etafilcon A SCL) and entered a CACE for 20 minutes. All subjects underwent tear osmolarity, tear evaporation rate, strip meniscometry, tear film breakup time, fluorescein vital staining, and functional visual acuity measurement before and after exposure to the controlled adverse chamber. Results. The mean blink rate increased with significant deteriorations in the mean symptom VAS scores, mean tear osmolarity, tear evaporation rate, strip meniscometry score, and tear stability with CACE exposure along with a decrease in visual maintenance ratio in functional visual acuity testing in etafilcon A wearers. The mean symptom VAS scores, mean tear evaporation rate, tear stability, blink rates, and visual maintenance ratios did not change significantly in narafilcon A wearers after CACE exposure. Conclusions. This study suggested marked tear instability, higher tear osmolarity, and increased tear evaporation with marked dry eye and visual symptomatology in nonadapted hydrogel SCL wearers, suggesting that silicone hydrogel SCLs may be suitable for persons who live and work in cool, low-humidity, and windy environments, as tested in this study. © 2011 The Association for Research in Vision and Ophthalmology, Inc.

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